Habibi Azam, Khosravi Amir, Soleimani Masoud, Nejabat Mahmood, Dara Mahintaj, Azarpira Negar
Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran.
Department of Tissue Engineering and Applied Cell Science, School of Advanced Technologies in Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
BMC Ophthalmol. 2025 May 20;25(1):299. doi: 10.1186/s12886-025-04078-9.
Sjögren's syndrome (SS) is a chronic inflammatory autoimmune disorder affecting salivary and lacrimal glands, leading to distressing ocular symptoms. Existing therapeutic approaches for SS-associated dry eye syndrome (DES) show insufficient efficacy. This study investigates the use of topical MSC-derived exosomes in primary SS-related DES.
In phase 1 and 2, triple-blinded, randomized trial, two vials of eye drops are given to each participant, one with code A and one with code B and only the supervisor knows the content of each vial. The treatment group (n = 8 eyes) received 10 µg of MSC-derived exosomes twice daily for two weeks and the control group (n = 8 eyes) received Phosphate buffered saline(PBS) for their respective eyes. Safety was assessed through ophthalmic exams, while DES assessment tests evaluated treatment effectiveness. Non-parametric tests employed to examine assumptions. The differences of ocular examination results between day 0 and month 3 were analyzed using a paired Student's t test. Measurement data that were not normally distributed are represented by the median (interquartile range), and comparisons were performed using the Wilcoxon rank-sum test.
The treatment showed promising results, with significant improvements observed in various indicators such as reduced Ocular Surface Disease Index scores, increased tear secretion, lower fluorescein scores, and longer tear-film break-up time before and after treatment and between the controls and the treated groups. Our results showed a significant increase in multifunctional proteins such as Epidermal Growth Factor and thrombospondin-1 and conversely, the levels of pro-inflammatory cytokines, including interleukin-6 and Matrix metalloproteinase-9 significantly decreased in tear of participant before and after treatment and between the controls and the treated groups.
Our study underscores the safety and substantial therapeutic potential of using MSC-derived extracellular exosomes eye drops to treat SS-associated DES.
IRCT20211102052948N1 The study protocol has been approved in Iranian Registry of Clinical Trials at 2022-04-20.
干燥综合征（SS）是一种慢性炎症性自身免疫性疾病，会影响唾液腺和泪腺，导致令人痛苦的眼部症状。现有的治疗与SS相关的干眼症（DES）的方法疗效不足。本研究调查了局部应用间充质干细胞衍生外泌体治疗原发性SS相关DES的效果。
在1期和2期双盲随机试验中，给每位参与者两瓶眼药水，一瓶编码为A，一瓶编码为B，只有监督者知道每瓶的内容。治疗组（n = 8只眼）每天两次接受10 µg间充质干细胞衍生外泌体治疗，持续两周，对照组（n = 8只眼）对各自的眼睛使用磷酸盐缓冲盐水（PBS）。通过眼科检查评估安全性，而DES评估测试则评估治疗效果。采用非参数检验来检验假设。使用配对学生t检验分析第0天和第3个月之间眼部检查结果的差异。非正态分布的测量数据用中位数（四分位间距）表示，并使用Wilcoxon秩和检验进行比较。
治疗显示出有前景的结果，在治疗前后以及对照组和治疗组之间，在各种指标上都观察到了显著改善，如眼表疾病指数评分降低、泪液分泌增加、荧光素评分降低以及泪膜破裂时间延长。我们的结果显示，表皮生长因子和血小板反应蛋白-1等多功能蛋白显著增加，相反，治疗前后以及对照组和治疗组之间参与者泪液中促炎细胞因子，包括白细胞介素-6和基质金属蛋白酶-9的水平显著降低。
我们的研究强调了使用间充质干细胞衍生的细胞外囊泡眼药水治疗SS相关DES的安全性和巨大治疗潜力。
IRCT20211102052948N1 该研究方案于2022年4月20日在伊朗临床试验注册中心获得批准。
